The Effect Of N-acetylcysteine On The Expression Of The Liver FGF21 In STZ-induced Diabetic Rats

Backgroud:The fibroblast growth factor 21(FGF21)is a member of fibroblast growth factor(FGF)family,it was first found in the mouse embryos by Nishimura and primarily expressed in the liver and adipose tissue,and excert beneficial effects on glucose and lipid metabolism through a way of endocrine, paracrine, autocrine as a secretory protein. Rencently,a study has proved that FGF21 is related with oxidative stress. N- acetylcysteine(NAC)can facilitate the synthsis of the glutathione,improve the organization of the glutathione inside the cellular, enhance the oxidative stress resistance ability of the tissue. Wether the NAC can regulate the expression of the FGF21 in the liver of the diabetic rats has not been reported. Objective:To investigate whether the NAC can regulate the expression of the FGF21 in the diabetic liver. Materials and Methods:1.We used STZ(45mg/kg)to established diabetic rats model.All the rats were randomly divided into three groups,including control group,diabetes group, DM with intervention of NAC group, we should observe 6 weeks and 12 weeks.2.Examine the general conditions and random blood glucose 、dyslipidemia、liver function index and the MDA、SOD in every groups periodically.3. Observe the position of the FGF21 expressed in the liver and the relative expression quantity between groups by immunohistochemical method.4. Detect the expression of protein FGF21 in the liver by Western Blot at the time of 6 weeks and 12 weeks.5.Using Real-time fluorescent quantitative PCR technique to detect the relative expression of the FGF21 m RNA in the liver at the time of 6weeks and 12 weeks. Results:1. We established type 1 diabetes mellitus model of the wistar rat successfully.2. With compared to the NC group.The rats of the DM group and NAC group drink more,have significant polyuria, polyphagia and angular symptoms, body weight decreased obviously(P<0.05), random blood glucose increased significantly(P<0.05).3. In contrast with NC group, the rats of DM group and NAC group have higher liver fuction index and more severe dyslipidemia(P<0.05),but the liver fuction index and dyslipidemia of the NAC intervention groupis better than the diabetes group。4.In comparison with NC group, the MDA level of the DM group and NAC group is significantly increased, and the SOD activity decreased significantly, diabetes group is more obvious.5. Immunohistochemical results show FGF21 expression in liver cell cytoplasm, rich in hepatic sinus surrounding. Compared with normal control group, diabetes group characterized by tan particles increased first then decreased;intervention group is characterized by tan particles increase gradually.6. The results of Western Blot showed that FGF21 expression quantity of DM group and NAC group at 6 weeks is significantly higher than the control group at the same period, with statistical significant(P < 0.05).FGF21 expression quantity after 12 weeks of DM group was obviously lower than the control group and intervention group in the same period,,whlie the FGF21 expression of the NAC intervention group at 12 weeks is higher than the control group,the difference is statistically significant(P< 0.05). And over time,the FGF21 protein expression in the diabetes group was raised at first, then decreased, while the FGF21 protein expression in the NAC intervention group showed a trend of rising.7. Real-time fluorescent quantitative PCR results showed that the FGF21 m RNA expression of the diabetes group at 6 week were higher than the NAC intervention group and the control group during the same period, the difference is statistically significant(P<0.05); the FGF21 m RNA expression of the DM group at the 12 weeks was obviously lower than the NAC group and control group in the same period and statistically significant difference(P<0.05). And over time,the FGF21 m RNA expression in the diabetes group and intervention group all show a trend of raised at first, then decreased.Conclusions :1. Diabetes can cause liver damage and cause imbalance of the oxidation system and the antioxidant defense system.2.The expression of FGF21 protein and FGF21 m RNA of the liver in control group between the 6 week and 12 week has no significant difference.3. Compared with normal control group, the relative expression of FGF21 m RNA of the liver of diabetes group and diabetes + NAC intervention group, all showed a trend of of first increasing and then decreasing.4. With longer duration of diabetes, the liver FGF21 protein expression quantity of diabetes group showed a trend of first rise then drop;while the FGF21 liver protein expression of the Intervention group showed a trend of rising.5. NAC may increase the expression of FGF21 protein in liver through resisting oxidative stress and protect the injury of the liver,and then ameliorate the dyslipidemia.